The Mechanism of Calcitonin Gene-Related Peptide^|^ndash;Containing Nerve Innervation

Abstract

Abstract. Calcitonin gene-related peptide (CGRP) is a major neurotransmitter and CGRPcontaining primary sensory neurons play an important role in nociception and potent vasodilation. CGRP-containing nerves in mesenteric arteries are decreased in pathological animal models (hypertension, diabetes, and atherosclerosis). In apolipoprotein E-knockout mice, which have atherosclerosis and peripheral sensory nerve defects, nerve growth factor (NGF)-mediated CGRP nerve facilitation was down-regulated, which may have been caused by the impairment of the Akt-NOcGMP pathway. In addition, NGF-mediated CGRP neurite outgrowth was decreased in fructoseinduced insulin-resistant rats. We recently discovered that renin-angiotensin inhibitors improved CGRP innervation in spontaneously hypertensive rats, indicating that rescuing CGRP nerve innervation might improve pathophysiological conditions. To find a novel reagent that facilitates CGRP nerves, a new model, phenol-injured perivascular nerve model rats, was established. Adrenomedullin, hepatocyte growth factor, and angiotensin II type 2 receptor activation induced CGRP nerve distribution in phenol-injured rats. Furthermore, in insulin-resistant model rats, the down-regulation of CGRP nerves was likely due to the depression of phosphoinositide 3-kinase (PI3K)-dependent Akt activation. Administration of candesartan improves CGRPergic function via the PI3K-Akt pathway in insulin-resistant rats. Thus, clarification of the mechanisms of CGRP nerve defects may constitute future therapeutic targets.

Differences in autonomic innervation to the vertebrobasilar arteries in spontaneously hypertensive and Wistar rats

“…We found no evidence of an increase in sensory fibre innervation in the adult SHR. Also we found no evidence of decreased CGRP functionality in the posterior cerebral arteries of adult SHR, as reported for dorsal root ganglia or mesenteric arteries (Supowit et al 2001;Hashikawa-Hobara et al 2012).…”

Effects of swimming exercise on nerve regeneration in a rat sciatic nerve transection model

“…CGRP is produced in both peripheral and central neurons and is a potent peptide vasodilator that can function in the transmission of pain [9]. In a spinal cord injury, CGRP is derived from motor neurons and plays a role in nerve regeneration after injury.…”

“…In a spinal cord injury, CGRP is derived from motor neurons and plays a role in nerve regeneration after injury. Conversely, CGRP is derived from dorsal root ganglion when synthesized in the dorsal horn of the spinal cord and may be involved in transmission of post-injury pain [9]. Previous studies showed that CGRP stimulates specific progenitor cells, which secrete an insulin-like growth factor, leading to regeneration [22], and CGRP represses specific immune cells, such as T lymphocytes, via repression of IL-2 and nuclear factor-kB [23].…”

“…To provide essential evidence, we assessed the influence of swimming following a 10-mm sciatic nerve defect in rats, which was repaired with a silicone rubber nerve tube. After a four-week recovery period, calcitonin gene-related peptide (CGRP) in the lumbar spinal cord, macrophage infiltration in the distal nerve end, and morphology and electrophysiology of the regenerated nerve in the tube were performed with the aim of elucidating the mechanisms underlying the observed effects of swimming [9]. …”

Heteroreceptors Modulating CGRP Release at Neurovascular Junction: Potential Therapeutic Implications on Some Vascular-Related Diseases

“…Using experimental models of hypertension, it has been reported that CGRP-containing nerves in mesenteric arteries are decreased [128]. In addition, capsaicin-induced hypertension can be mediated by decreased vasodilatation (CGRP, kinin, or prostaglandin) or by a direct action on vascular smooth muscle [129].…”